| Micronized particulate pharmaceutical materials prepared using dense gas antisolvent precipitation is of great advantage over traditional micronization techniques in terms of particle size distribution and reproducibility. Our work shows that spherical particles with different degrees of agglomeration can be produced under mild operating conditions. These results stimulate further studies on the structure-property relationship of the precipitates.;Preliminarily, we performed dense gas antisolvent precipitation on a number of polymers of pharmaceutical interest, including poly(DTE carbonate) and polyvinylpyrrolidone (PVP) with different molecular weights. We explored the effect of experimental conditions on the particle size and morphology. For poly (desamino tyrosyl-tyrosine alkyl ester carbonate) [poly(DTE carbonate)], its microparticles with controlled size could be applied in the field of tissue engineering, which could facilitate better exertion of the biochemical functions of this biodegradable polymer. On the other hand, PVPs are common excipients widely used in pharmaceutical formulation development. Physicochemical properties of both types of polymers provide flexibility of their application. Their precipitation by dense gas as antisolvent provided informative data for subsequent experiment of forming solid dispersions.;Solid dispersions were prepared by precipitation of PVP with several pharmaceutical compounds using dense gas carbon dioxide as antisolvent. We focused on the morphology and particle size control of the products for the first two model drugs, prednisolone and its acetate salt, and then we prepared solid dispersions of a nonsteroidal anti-inflammatory drug, piroxicam. Microcrystals or microspheres were formed where the drug was amorphously dispersed in the polymeric matrix, with drug loadings dependent on initial drug-polymer weight ratios. The existence of interaction between the drug and polymer was confirmed through characterization of their physicochemical properties. The dissolution profiles of solid dispersions showed significant improvement in the dissolution rate of piroxicam compared with their corresponding physical mixtures and plain drug. These results manifest the great potential of this dense gas technique in improving bioavailability of water-insoluble pharmaceutical substances. |
